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Neurochem Int. 2010 Dec;57(7):844-50. doi: 10.1016/j.neuint.2010.09.001. Epub 2010 Sep 16.

Heat shock protein 70 upregulation by geldanamycin reduces brain injury in a mouse model of intracerebral hemorrhage.

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  • 1Department of Physiology, Loma Linda University, Loma Linda, CA 92350, USA.

Abstract

This study investigated the effect of geldanamycin post-treatment on the development of secondary brain injury and neurological deficits in a mouse model of intracerebral hemorrhage. CD-1 mice received stereotactic injection of collagenase type VII into the right basal ganglia. Treatment groups were administered 1 mg/kg (low dose) or 10 mg/kg (high dose) of geldanamycin. Mice were euthanized at two time-points: 24 h or 72 h. Blood-brain-barrier permeability, brain edema, and neurobehavioral deficits were assessed. Additionally, the effects of geldanamycin on heat shock protein 27 and 72; tumor necrosis factor-alpha and interleukin 1 beta expressions were evaluated. High dose geldanamycin significantly attenuated blood-brain barrier disruption and brain edema after intracerebral hemorrhage. Neurobehavioral outcomes were significantly improved in some parameters by high dose treatment. Molecular results showed a marked increase in heat shock protein 72 expression in ipsilateral brain of geldanamycin treated groups with a reduction in the pro-inflammatory tumor necrosis factor-alpha.

CONCLUSION:

Geldanamycin post-treatment is neuroprotective in the mouse model of intracerebral hemorrhage. Geldanamycin administration results in reduction of inflammation, preservation of blood-brain-barrier and amelioration of neurobehavioral deficits after an insult possibly by upregulation of heat shock protein 72.

Copyright © 2010 Elsevier Ltd. All rights reserved.

PMID:
20849898
[PubMed - indexed for MEDLINE]
PMCID:
PMC2965477
Free PMC Article
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